Dickkopf-1 Levels in Turkish Patients with Bladder Cancer and its Association with Clinicopathological Features (original) (raw)
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Serum Dickkopf-1 as A Biomarker for The Diagnosis and Prognosis of Hepatocellular Carcinoma
2019
Background: Hepatocellular carcinoma is one of the commonest cancers in world. It is one of the major health problems and its incidence is increasing. The main routinely used parameter for diagnosis of HCC is AFP, also it can be elevated in the liver cirrhosis. It represents a liver cell specific, not a tumor specific marker, for these reasons, we suggest use AFP as a supplementary marker for HCC diagnosis. So, identification of a sensitive biomarker to improve early diagnosis of HCC is in need. Aim of the work: this study was aimed to evaluate the clinical significance of serum Dickkopf-1 (DKK1) as a diagnostic and prognostic marker in hepatocellular carcinoma. Patients and Methods: in this study 100 subjects were included and divided into 3 groups, Group I: included 50 patients with HCC, and divided into 2 subgroups according to Barcelona Clinic Liver Cancer (BCLC) into early HCC (24 patients) and late HCC (18 patients). Group II: included 25 patients with liver cirrhosis. Group III: included 25 healthy subjects (control). Clinical assessment, routine laboratory evaluation, CT scan and measurements of serum alpha-fetoprotein (AFP) and DKK1 were performed to all patients and repeated to group I patients 1 month after treatment. Results: the current study showed that Serum DKK1 was significantly elevated in HCC group compared to liver cirrhosis and healthy control groups, with increased level in late than early stage. The optimum cut off values of DKK1 for diagnosis of HCC was 1.92 ng/mL (AUC 0.926, sensitivity 88% and specificity 83%). While the optimum cut off value for AFP was 102 ng/mL (AUC 0.904, 71% sensitivity and 84% specificity). Testing of both serum DKK1 and AFP increased the diagnostic accuracy for HCC (AUC 0.964, sensitivity 91%, and specificity 90%). Serum DKK1 level significantly decreases after HCC treatment with radio-frequency ablation. Conclusion: It could be concluded that Testing of both serum DKK1 and AFP significantly increased the diagnostic accuracy for HCC. Meanwhile, DKK1 can be used alone for diagnosis of HCC even in HCC with inconclusive AFP. Serum DKK1 might be a potential diagnostic and prognostic marker for HCC.
ASSESSMENT OF DICKKOPF-1 AS A BIOMARKER OF HEPATOCELLULAR CARCINOMA IN EGYPTIANS.
International Journal of Advanced Research (IJAR), 2019
Background: Hepatocellular carcinoma (HCC) is considered to be one of the most aggressive malignancies. Several studies have shown that dickkopf-1 (DKK1) is overexpressed in HCC tissue. Objective and Methods: The present study aimed at demonstrating the diagnostic efficacy of serum levels of DKK1 in HCC in comparison to alpha fetoprotein (AFP). Eighty individuals were included in the present study, and categorized to three groups: Group I: 40 patients with HCC on top of viral liver cirrhosis, Group II: 20 patients with viral induced liver cirrhosis without HCC, and Group III: 20 healthy individuals. Serum levels of AFP and DKK1 were measured and compared in all groups. Results:The values of AFP and DKK1 in group I were statistically higher than those in groups II and III. At the optimum value of 11.7 ng/ml, the sensitivity and specificity of serum AFP were 70.0% and 87.5%, respectively. DKK1 had higher sensitivity (80.0%) and specificity (90.0%) than AFP, at the cut-off value of 1.28 ng/ml for the diagnosis of HCC. Area under the curve (AUC) was higher in DKK1 (0.811) than AFP (0.779) when discriminating between group I and other groups. It was noted that the combination of both markers had a higher sensitivity and specificity, and a larger AUC than each alone. Conclusion: Serum DKK1 is a promising biomarker and is superior to AFP for HCC diagnosis. Combination of AFP and DKK1 improved the accuracy of HCC diagnosis in relation to each test alone.
Elevated levels of Dickkopf-related protein 3 in seminal plasma of prostate cancer patients
Journal of Translational Medicine, 2011
Background: Expression of Dkk-3, a secreted putative tumor suppressor, is altered in age-related proliferative disorders of the human prostate. We now investigated the suitability of Dkk-3 as a diagnostic biomarker for prostate cancer (PCa) in seminal plasma (SP). Methods: SP samples were obtained from 81 patients prior to TRUS-guided prostate biopsies on the basis of elevated serum prostate-specific antigen (PSA; > 4 ng/mL) levels and/or abnormal digital rectal examination. A sensitive indirect immunoenzymometric assay for Dkk-3 was developed and characterized in detail. SP Dkk-3 and PSA levels were determined and normalized to total SP protein. The diagnostic accuracies of single markers including serum PSA and multivariate models to discriminate patients with positive (N = 40) and negative (N = 41) biopsy findings were investigated. Results: Biopsy-confirmed PCa showed significantly higher SP Dkk-3 levels (100.9 ± 12.3 vs. 69.2 ± 9.4 fmol/mg; p = 0.026). Diagnostic accuracy (AUC) of SP Dkk-3 levels (0.633) was enhanced in multivariate models by including serum PSA (model A; AUC 0.658) or both, serum and SP PSA levels (model B; AUC 0.710). In a subpopulation with clinical follow-up > 3 years post-biopsy to ensure veracity of negative biopsy status (positive biopsy N = 21; negative biopsy N = 25) AUCs for SP Dkk-3, model A and B increased to 0.667, 0.724 and 0.777, respectively. Conclusions: In multivariate models to detect PCa, inclusion of SP Dkk-3 levels, which were significantly elevated in biopsy-confirmed PCa patients, improved the diagnostic performance compared with serum PSA only.
Virchows Archiv, 2018
In this collaborative study by the Russian Society of Clinical Oncology and the Russian Society of Pathology, we assessed the concordance among three validated, commercially available PD-L1 immunohistochemistry assays for patients with urothelial cancer. Tumors from 100 urothelial cancer patients were stained with the antibody clones 22C3 (Agilent), SP142 (Ventana Medical Systems), and SP263 (Ventana Medical Systems), which are used in clinical trials of second-line therapy with checkpoint inhibitors. Four trained pathologists independently evaluated the percentages of tumor cells (TC) and tumor-infiltrating immune cells (IC) that were stained at any intensity by each of the antibodies. The test-specific cutoffs for the proportions of stained cells in a positive sample were pre-specified as TC + IC ≥ 10% or TC ≥ 10% for 22C3, IC ≥ 5% for SP142, and TC ≥ 25% or IC ≥ 25% for SP263. Three hundred immunohistochemistry slides were scored. The percentages of PD-L1 staining in the three assays without using any cutoff were higher in the IC than in the TC (55% versus 24% for 22C3, 45% versus 8% for SP142, and 72% versus 27% for SP263, respectively). The Pearson correlation coefficients for anti-PD-L1 staining in the IC were 0.5, 0.69, and 0.85 with 22C3/SP142, 22C3/SP263, and SP142/SP263, respectively. The Pearson correlation coefficients for PD-L1 staining in the TC were 0.93, 0.99, and 0.91 for the same pairs. Among the patients who were negative for PD-L1 staining by one test, 91-100% were also negative by the other tests. Among the patients who were positive by one test, 43-100% were also positive by the other tests. Our data indicate that repeated testing can be avoided as a patient with urothelial cancer who is classified as negative for PD-L1 expression by one of the three single tests using the corresponding cutoff rule is highly likely (91-100%) to be classified as negative by either of the other tests.
DKK-1 in prostate cancer diagnosis and follow up
BMC Clinical Pathology, 2014
Background: Dickoppf-1 (DKK-1) is a negative regulator of bone formation with tumorigenic potential. The up-regulation of DKK-1 is an early event in prostate cancer (PCa) development, thus we investigated its role as a marker in the diagnosis and prognosis of PCa. Methods: We retrospectively enrolled 159 patients who underwent prostate biopsy, either for elevated PSA or suspect digital rectal examination, between 2003 and 2010. During the biopsy, one serum sample was collected from all patients; PSA and DKK-1 were measured by ELISA technique. Amongst the biopsy of 159 patients 75 were affected by PCa and 84 were not the mean period of follow-up for these patients was 5 years; a new biopsy was performed in case of PCa suspicion. Results: PSA performed better than DKK-1 in detecting PCa (0.63 vs 0.51 respectively). Differently from PSA DKK-1 was significantly higher in patients who developed PCa during follow-up than in cancer-free ones, thus DKK-1 performed better than PSA in detecting these patients (0.67 vs 0.55). DKK-1 was significantly lower in patients with bone metastases, whereas PSA was not significantly different in patients with different outcomes. Conclusions: DKK-1 might be predictive for patients negative at first biopsy who will develop PCa and in the prognosis of bone metastases. It performed worse than PSA in the early diagnosis of Pca.
Molecular markers in bladder cancer
Current Opinion in Urology, 2008
Purpose Use of molecular markers in urine, tissue or blood offers potential opportunities to improve understanding of bladder cancer biology which may help identify disease earlier, risk stratify patients, improve prediction of outcomes or help target therapy. Methods A review of the published literature was performed, without restriction of time. Results Despite the fast-growing literature about the topic and the approval of several urinary biomarkers for use in clinical practice, they have not reached the level of evidence for widespread utilization. Biomarkers could be used in different clinical scenarios, mainly to overcome the limitations of current diagnostic, predictive, and prognostic tools. They have been evaluated to detect bladder cancer in asymptomatic populations or those with hematuria and in surveillance of disease as adjuncts to cystoscopy. There is also a potential role as prognosticators of disease recurrence, progression and survival both in patients with non-invasive cancers and in those with advanced disease. Finally, they promise to be helpful in predicting the response to local and/or systemic chemotherapy and/or immunotherapy. Conclusions To date, due to the lack of high-quality prospective trials, the level of evidence provided by the current literature remains low and, therefore, the potential of biomarkers exceeds utilization in clinical practice.
International journal of advanced research in medicine, 2023
Background: Liver cancer is the fifth most common cancer and the second most frequent cause of cancer-related death globally. Diagnosis of hepatocellular carcinoma (HCC) should occur in an early stage, so that the patient benefits from earlier diagnosis, through treatment using established algorithms. The research aimed to evaluate the significance of Dickkopf-1 (DKK1) as a tumor biomarker for the diagnosis and prognosis of HCC in cirrhotic cases. Methods: This prospective, randomized, controlled research was carried out on 120 individuals who were classified as follow: Group I: comprised 40 cases with cirrhotic liver and HCC. Group II: comprised 30 cases with cirrhotic liver without HCC. Group III: comprised 30 cases with chronic hepatitis without cirrhosis. Control group: comprised 20 healthy individuals. Serum DKK-1 level were measured to all participants but for HCC patient group it was measured before intervention and one month after intervention (with the first CT after intervention). Results: Six cases of group I underwent microwave ablation, 13 cases underwent RFA, 20 cases underwent trans-arterial chemotherapy (TACE) and one patient underwent liver transplantation. Thirteen cases of group I were well ablated following loco regional therapy and no recurrence or de novo lesions appeared during follow up. Residual activity or de novo lesions or recurrence appeared in 26 cases who required second cession of ablation. alpha-fetoprotein (AFP) in group I was ranging between 3.6 to 2400 ng/ml with mean 698.870 ng/ml. It was higher in group I than groups II, III, and IV. DKK1 level was significantly higher in group I than groups II, III and IV, also, was significantly higher in group II than groups III and IV and it was significantly higher in group III than group IV. Conclusions: Serum DKK1 could serve as a potential diagnostic biobiomarker for HCC. DKK1 might be utilised as a predictor of therapeutic ablation outcome in cases with hepatocellular carcinoma.
Oncotarget, 2015
To identify whether Dickkopf-1 (DKK1) could be a potential biomarker for early detection and prognosis in patients with pancreatic cancer (PC). Serum was collected from 140 patients with pancreatic adenocarcinoma and 92 control patients without pancreatic adenocarcinoma. Serological levels of DKK1 were examined by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity was compared with carbohydrate antigen 19-9 (CA19-9). A 2-year follow-up was monitored to evaluate the correlation between DKK1 serum levels and overall survival. The expression of DKK1 in PC tumor tissues was also evaluated using immunohistochemistry staining. Serum levels of DKK1 and CA19-9 were elevated in PC patients in the early-stage cases. These levels increased with the advancement of clinical stage. There was significant difference in DKK1 serum levels between early and advanced PC stages. Receiver operating characteristic curve (ROCC) analysis showed that DKK1 was significantly better than...
Dickkopf-1: As a Diagnostic and Prognostic Serum Marker for Hepatocellular Carcinoma
2016
Background and study aim: Hepatocellular carcinoma (HCC) accounts for 70-80% of all liver cancers and the 5-year survival is only 3-5%. This bad prognosis is due to the lack of an effective method for early diagnosis. So, only 30-40% of patients with HCC are suitable for curative treatments at the time of diagnosis. Thus, there is a great need for tools to diagnose HCC early especially in cirrhotic patients. The aim of this work is to assess the validity of serum DKK1 as a diagnostic marker for HCC and to assess prognostic value of serum DKK1 in predicting treatment response, complication and survival in HCC patients. Patients and Methods: This study included 60 Patients divided into two groups. Group A: consisted of 30 patients with post hepatitic C and/or B liver cirrhosis. Group B: consisted of 30 patients with HCC on top of post hepatitic C and/or B liver cirrhosis. Group B patients underwent either radiofrequency ablation or ethanol injection. Clinical assessment, routine laboratory evaluation, CT studies and measurement of serum alpha-fetoprotein (AFP) and DKK1 were performed to all patients and repeated to group B patients 1 and 3 months after treatment. Results: The optimum cut off value of DKK1 for diagnosis of HCC was 4.3 ng/mL (AUC 0.89, sensitivity 66.7% and specificity 96.6%) (P<0.001). While, the optimum cut off value for AFP was > 101 ng/mL with 90% sensitivity and 75.9% specificity (p<0.001). Testing of both DKK1 and AFP increased the diagnostic accuracy for HCC (AUC 0.901, sensitivity 93.3%, and specificity 75.9) (P<0.001). Serum DKK1 level significantly decreases after HCC treatment with either radiofrequency ablation or ethanol injection (P<0.001). Conclusion: Testing of both DKK1 and AFP significantly increased the diagnostic accuracy for HCC. Meanwhile, DKK1 can be used alone for HCC diagnosis even in HCC with inconclusive AFP. DKK1 has a promising prognostic value and can be used for follow up of HCC patients who underwent loco-regional treatment.